Clonal selection of stable aneuploidies in progenitor cells drives high-prevalence tumorigenesis.

Chromosome gains and losses are a frequent feature of human cancers. However, how these aberrations can outweigh the detrimental effects of aneuploidy remains unclear. An initial comparison of existing chromosomal instability (CIN) mouse models suggests that aneuploidy accumulates to low levels in these animals. We therefore developed a novel mouse model that enables unprecedented levels of chromosome missegregation in the adult animal. At the earliest stages of T-cell development, cells with random chromosome gains and/or losses are selected against, but CIN eventually results in the expansion of progenitors with clonal chromosomal imbalances. Clonal selection leads to the development of T-cell lymphomas with stereotypic karyotypes in which chromosome 15, containing the Myc oncogene, is gained with high prevalence. Expressing human MYC from chromosome 6 (MYCChr6) is sufficient to change the karyotype of these lymphomas to include universal chromosome 6 gains. Interestingly, while chromosome 15 is still gained in MYCChr6 tumors after genetic ablation of the endogenous Myc locus, this chromosome is not efficiently gained after deletion of one copy of Rad21, suggesting a synergistic effect of both MYC and RAD21 in driving chromosome 15 gains. Our results show that the initial detrimental effects of random missegregation are outbalanced by clonal selection, which is dictated by the chromosomal location and nature of certain genes and is sufficient to drive cancer with high prevalence.

Association of 20-Year Longitudinal Depressive Symptoms With Left Ventricular Geometry Outcomes in the Coronary Artery Risk Development in Young Adults Study: A Role for Androgens?

OBJECTIVE: Depression is a risk factor for coronary heart disease and left ventricular hypertrophy (LVH) is a potent predictor of coronary heart disease events. Whether depression is associated with LVH has received limited investigation. This study assessed cross-sectional and 20-year longitudinal associations of depressive symptoms with LVH outcomes after accounting for important known confounders. METHODS: From 5115 participants enrolled in 1985-1986 in the Coronary Artery Risk Development in Young Adults Study, 2533 had serial measures of depressive symptoms and subsequent echocardiography to measure normal LV geometry, concentric remodeling, and LVH. The primary exposure variable was trajectories of the Center for Epidemiologic Studies Depression (CES-D) scale score from 1990-1991 to 2010-2011. Multivariable polytomous logistic regression was used to assess associations of trajectories with a composite LV geometry outcome created using echocardiogram data measured in 2010-2011 and 2015-2016. Sex-specific conflicting results led to exploratory models that examined potential importance of testosterone and sex hormone-binding globulin. RESULTS: Overall CES-D and Somatic subscale trajectories had significant associations with LVH for female participants only. Odds ratios for the subthreshold (mean CES-D ≈ 14) and stable (mean CES-D ≈ 19) groups were 1.49 (95% confidence interval = 1.05-2.13) and 1.88 (95% confidence interval = 1.16-3.04), respectively. For female participants, sex hormone-binding globulin was inversely associated with LVH, and for male participants, bioavailable testosterone was positively associated with concentric geometry. CONCLUSIONS: Findings from cross-sectional and longitudinal regression models for female participants, but not male ones, and particularly for Somatic subscale trajectories suggested a plausible link among depression, androgens, and LVH. The role of androgens to the depression-LVH relation requires additional investigation in future studies.

Multilevel perspectives on the implementation of the collaborative care model for depression and anxiety in primary care.

BACKGROUND: The Collaborative Care Model (CoCM) is an evidence-based mental health treatment in primary care. A greater understanding of the determinants of successful CoCM implementation, particularly the characteristics of multi-level implementers, is needed. METHODS: This study was a process evaluation of the Collaborative Behavioral Health Program (CBHP) study (NCT04321876) in which CoCM was implemented in 11 primary care practices. CBHP implementation included screening for depression and anxiety, referral to CBHP, and treatment with behavioral care managers (BCMs). Interviews were conducted 4- and 15-months post-implementation with BCMs, practice managers, and practice champions (primary care clinicians). We used framework-guided rapid qualitative analysis with the Consolidated Framework for Implementation Research, Version 2.0, focused on the Individuals domain, to analyze response data. These data represented the roles of Mid-Level Leaders (practice managers), Implementation Team Members (clinicians, support staff), Innovation Deliverers (BCMs), and Innovation Recipients (primary care/CBHP patients) and their characteristics (i.e., Need, Capability, Opportunity, Motivation). RESULTS: Mid-level leaders (practice managers) were enthusiastic about CBHP (Motivation), appreciated integrating mental health services into primary care (Need), and had time to assist clinicians (Opportunity). Although CBHP lessened the burden for implementation team members (clinicians, staff; Need), some were hesitant to reallocate patient care (Motivation). Innovation deliverers (BCMs) were eager to deliver CBHP (Motivation) and confident in assisting patients (Capability); their opportunity to deliver CBHP could be limited by clinician referrals (Opportunity). Although CBHP alleviated barriers for innovation recipients (patients; Need), it was difficult to secure services for those with severe conditions (Capability) and certain insurance types (Opportunity). CONCLUSIONS: Overall, respondents favored sustaining CoCM and highlighted the positive impacts on the practice, health care team, and patients. Participants emphasized the benefits of integrating mental health services into primary care and how CBHP lessened the burden on clinicians while providing patients with comprehensive care. Barriers to CBHP implementation included ensuring appropriate patient referrals, providing treatment for patients with higher-level needs, and incentivizing clinician engagement. Future CoCM implementation should include strategies focused on education and training, encouraging clinician buy-in, and preparing referral paths for patients with more severe conditions or diverse needs. TRIAL REGISTRATION: ClinicalTrials.gov(NCT04321876). Registered: March 25,2020. Retrospectively registered.

Psychologists and Integrated Behavioral Health Simulation Training: A Survey of Medical Educators and Perspectives of Directors of Clinical Training.

It is well established that the integration of behavioral healthcare into the medical home model improves patient outcomes, reduces costs, and increases resident learning. As academic health centers increasingly integrate behavioral healthcare, targeted training for interprofessional collaboration around behavioral healthcare is needed. Simulation educational approaches potentially can provide this training. Health service psychologists are well-poised to support this because of their specialized training in integrated healthcare. The present exploratory study aimed to evaluate existing simulation programs and develop recommendations for integrated behavioral health training and evaluation. Directors of ACGME accredited residency programs that are high utilizers of the medical home model (Pediatrics, Internal Medicine, Medicine/Pediatrics, Family Medicine) as well as Psychiatry residencies and medical schools with membership in the Society for Simulation in Healthcare were recruited to complete a 26-item survey to assess program usage of psychologists as part of simulation training for integrated behavioral healthcare services. Of 79 participants who completed initial items describing their training program, only 32 programs completed the entire survey. While many academic health centers offered integrated team and behavioral health simulations, few utilized psychology faculty in design, implementation, and evaluation. Other behavioral health providers (psychiatrists, social workers) were often involved in medical school and pediatric residency simulations. Few institutions use standardized evaluation. Qualitative feedback and faculty-written questionnaires were often used to evaluate efficacy. Survey responses suggest that psychologists play limited roles in integrated behavioral healthcare simulation despite their expertise in interdisciplinary training, integrated behavioral healthcare, and program evaluation.

Nutrition Literacy Is Not Sufficient to Induce Needed Dietary Changes in Nonalcoholic Fatty Liver Disease.

INTRODUCTION: Dietary and lifestyle changes are the first line of therapy for nonalcoholic fatty liver disease (NAFLD), the most prevalent liver disease in the western world. Nutrition literacy is the ability to understand nutrition information and implement that knowledge. We aimed to compare indicators of nutrition literacy in subjects with and without NAFLD in a representative US cohort. METHODS: In a cross-sectional study using data from the National Health and Nutrition Examination Survey 2017-2018 cycle, we included 2,938 adult subjects with complete dietary and vibration-controlled transient elastography data and no alternative reason for hepatic steatosis. Nutrition literacy was assessed using questionnaires. Diet perception accuracy was assessed by comparing self-reported diet quality with objective diet quality scores-the Healthy Eating Index and alternative Mediterranean diet score-to assess real-world application of nutrition knowledge. RESULTS: Nutrition literacy was not different between subjects with or without NAFLD ( P = 0.17): more than 90% of subjects reported using nutrition labels, and most of them correctly identified the meaning of daily value. Subjects with NAFLD had a lower-quality diet (Healthy Eating Index, P = 0.018; alternative Mediterranean diet, P = 0.013) and rated their diet as poorer ( P < 0.001). On self-assessment, only 27.8% of subjects overestimated their diet quality, while 37.5% consumed more calories than their self-assessed needs. Both accuracy measures were similar between subjects with NAFLD and those without ( P = 0.71 and 0.63, respectively). Subjects with NAFLD were more likely to report being advised to lose weight (42.1% vs 16.5%, P < 0.001) or to attempt losing weight (71.9% vs 60.9%, P < 0.001). Diet quality was not better in subjects with NAFLD who received dietary recommendations. DISCUSSION: Subjects with NAFLD have poor diet quality despite receiving medical recommendations to lose weight and having nutrition literacy and perception that are comparable with subjects without NAFLD. Educational approaches may not be sufficient to promote weight loss and improve diet quality in NAFLD.

Implementation Barriers and Experiences of Eligible Patients Who Failed to Enroll in Collaborative Care for Depression and Anxiety.

BACKGROUND: Effective and efficient implementation of the Collaborative Care Model (CoCM) for depression and anxiety is imperative for program success. Studies examining barriers to implementation often omit patient perspectives. OBJECTIVES: To explore experiences and attitudes of eligible patients referred to CoCM who declined participation or were unable to be reached, and identify implementation barriers to inform strategies. DESIGN: Convergent mixed-methods study with a survey and interview. PARTICIPANTS: Primary care patients at an academic medical center who were referred to a CoCM program for anxiety and depression by their primary care clinician (PCC) but declined participation or were unable to be reached by the behavioral health care manager to initiate care (n = 80). Interviews were conducted with 45 survey respondents. MAIN MEASURES: Survey of patients' referral experiences and behavioral health preferences as they related to failing to enroll in the program. Interview questions were developed using the Consolidated Framework for Implementation Research version 2.0 (CFIR 2.0) to identify implementation barriers to enrollment. KEY RESULTS: Survey results found that patients were uncertain about insurance coverage, did not understand the program, and felt services were not necessary. Referred patients who declined participation were concerned about how their mental health information would be used and preferred treatment without medication. Men agreed more that they did not need services. Qualitative results exhibited a variety of implementation determinants (n = 23) across the five CFIR 2.0 domains. Barriers included mental health stigma, perceiving behavioral health as outside of primary care practice guidelines, short or infrequent primary care appointments, prioritizing physical health over mental health, receiving inaccurate program information, low motivation to engage, and a less established relationship with their PCC. CONCLUSIONS: Multiple barriers to enrollment led to failing to link patients to care, which can inform implementation strategies to address the patient-reported experiences and concerns.

TIPS: indications, Contraindications, and Evaluation.

PURPOSE OF REVIEW: This review summarizes the current and emerging indications, contraindications, and evaluation for TIPS. In the last three decades of use, there have been substantial changes and progress in this field, including the use of controlled-expansion, covered stents, which has broadened the clinical uses of TIPS. RECENT FINDINGS: Recent findings have rapidly expanded the indications for TIPS, including emerging uses in hepatorenal syndrome, hepatopulmonary syndrome and before abdominal surgery. The widespread use of controlled-expansion, covered stents has decreased rates of post-TIPS hepatic encephalopathy, opening TIPS to a larger patient population. Overall, with newer stent technology and more research in this area, the clinical utility and potential of TIPS has rapidly expanded. Going forward, a renewed focus on randomized-control trials and long-term outcomes will be a crucial element to selecting appropriate TIPS recipients and recommending emerging indications for this procedure.

Organ Donation in Canadian PICUs: A Cross-Sectional Survey, 2021-2022.

OBJECTIVES: To understand contemporary pediatric organ donation programs in Canadian PICUs, including: policies and practices, data collection and reporting, and system and process barriers. DESIGN: A cross-sectional survey carried out 2021-2022. SETTING: Canadian PICUs affiliated with a donor physician network. SUBJECTS: Pediatric intensivists identified as the donation program lead, or most knowledgeable about donation for their institution. MEASUREMENTS AND MAIN RESULTS: A 19-item survey was developed through collaboration with stakeholders from the organ donation and transplantation community within Canada. Domains and items were generated and reduced iteratively during an in-person workshop. Pretesting and pilot testing were completed to ensure readability, flow, clinical sensibility, and construct validity. Fifteen of 16 (94%) invited Canadian PICUs from seven provinces completed the survey representing 88% (15/18) of all noncardiac Canadian PICUs. Surveys were completed between June 2021 and September 2022. All units support donation after death by neurologic criteria (DNC); 14 of 15 indicated donation policies were in place and 1 of 15 indicated no policy but the ability to facilitate donation. Thirteen of 15 units (87%) support donation after death by circulatory criteria (DCC) with policies in place, with 11 of 13 of these indicating routine support of donation opportunities. The majority (13/15) of units identified a donation champion. Of the 16 identified champions across these centers, 13 were physicians and were registered nurses or nurse practitioners. Eight of 13 units (62%) with donation champions had positions supported financially, of which 5 units came from the Organ Donation Organization and the other 3 came from the provincial health authority. Finally, only 3 of 15 PICU donation programs have a pediatric donation committee with family involvement. Variability exists in identification (including determination of death practices), referral, and approach for donation between units. CONCLUSIONS: Although all Canadian PICUs support donation after DNC donation, and most support donation after DCC, variability exists in the identification, referral, and approach of potential donors. There is a notable lack of family involvement in pediatric donation programs. There are many opportunities for standardization of PICU donation programs which may result in improved rates of pediatric organ donation in Canada.

Depressive Symptom Subgroups and Their Association with Prevalent and Incident Cardiovascular Risk Factors in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

BACKGROUND: We sought to identify depressive symptom subgroups in a community sample of young adults, investigate their stability over time, and determine their association with prevalent and incident cardiovascular disease (CVD) risk factors. METHOD: Participants were 3377 adults from the Coronary Artery Risk Development in Young Adults study. Using latent class and latent transition analysis, we derived subgroups based on items of the 20-item version of the Center for Epidemiologic Studies Depression Scale in 1990, and examined patterns of change over a 10-year period (1990-2000). Cox regression models were used to examine associations between subgroup membership and prevalent (2000) and incident (2000 to 2016) obesity, hypertension, and diabetes. RESULTS: Three baseline subgroups were identified and labeled: "No Symptoms" (63.5%), "Lack of Positive Affect" (PA, 25.6%), and "Depressed Mood" (10.9%). At 10-year follow-up, individuals in "No Symptoms" subgroup had the highest probability (0.84) of being classified within the same subgroup. Participants classified as "Lack of PA" were likely (0.46) to remain in the same subgroup or be classified as "No Symptoms." Participants in the "Depressed Mood" were most likely to transition to the "Lack of PA" subgroup (0.38). Overall, 30.5% of participants transitioned between subgroups, with 11.4% classified as "Worsening" and 19.1% as "Improving." Relative to the "No Symptoms Stable," other subgroups ("Depressed Stable," "Worsening," and "Improving") were associated with prevalent obesity and hypertension. CONCLUSION: We identified distinct depressive symptom subgroups that are variably stable over time, and their change patterns were differentially associated with CVD risk factor prevalence.

Perspectives of Primary Care Clinicians on the Diagnosis and Treatment of Pediatric Hypertension.

The purpose of this study was to contextualize the challenges of diagnosing and managing pediatric hypertension (pHTN) in federally qualified health centers. We conducted a survey among primary care clinicians (N = 72) who treat children (3-17 years old) in a national network of health centers. Clinicians reported practices of blood pressure (BP) measurement, barriers to diagnosis and management of pHTN, and use of population health tools. Most clinicians (83%) used electronic devices to measure BP, only 49% used manual BP readings for follow-up measurements, and more than half measured BP at each encounter. The highest-rated barrier to pHTN management was lack of comfort with antihypertensive medications (71% of respondents). Few clinicians (10%) had used population health tools, but most (78%) indicated they would like to use them for pHTN. These results offer clinician-level insights regarding implementation of the pHTN guideline in pediatric primary care settings.

Baseline Targeted Moderation in a Trial of the Family Check-Up 4 Health: Potential Explanations for Finding Few Practical Effects.

Not all participants will benefit equally from even well-established, evidence-based prevention programs. For this reason, the field of prevention science is beginning to embrace individual tailoring of interventions. The Family Check-Up was among the first prevention programs to tailor at the family level as opposed to the more prevalent focus on adapting programs for different cultures, genders, and other immutable participant characteristics. Despite tailoring, families with lower levels of stress and parental mental health issues, children with lower baseline conduct problems, and families living in an extremely deprived neighborhood benefitted less from the Family Check-Up. This study examined baseline targeted moderation (BTM) within a trial of the Family Check-Up 4 Health (FCU4Health) program, an adaptation of the Family Check-Up for primary care delivery and explicit targeting of obesogenic behaviors. Ethnically diverse, low-income families (N = 240) with children ages 5.5 to 12 years identified in pediatric primary care with elevated body mass index (BMI) were enrolled and randomized to FCU4Health or usual care. Few BTM effects were found using single-variable-as-moderator and latent-class-as-moderator analytic approaches across the primary (child BMI, body composition) and secondary outcomes (family health routines; child eating behaviors, food choices, emotional problems, problem behaviors, quality of life; caregiver BMI and body composition), as well as hypothesized mediators (child self-regulation, parenting skills). The high-risk nature of the sample and the FCU4Health being individually tailored might have mitigated finding BTM effects. This trial was prospectively registered (NCT03013309 ClinicalTrials.gov).

Research engagement and experiences of patients pre- and post-implant of a left ventricular assist device from the mechanical circulatory support measures of adjustment and quality of life (MCS A-QOL) study.

PURPOSE: Adults living with mechanical circulatory support (MCS) present with unique challenges (e.g., left ventricular assist device [LVAD]-related self-care, adverse events) to research study enrollment, engagement, and completion. The purpose of this study was to understand the experiences of adults with MCS who were eligible for and enrolled in a study of health-related quality of life (HRQOL). METHODS: In a secondary analysis of data from the Mechanical Circulatory Support: Measures of Adjustment and Quality of Life study, we used a mixed-methods approach to evaluate research engagement and experiences among adults preparing to undergo or currently living with MCS implant. First, we assessed the cascade of study engagement. Second, we assessed research experiences using a structured interview developed for this study. RESULTS: Of 1011 participants approached for the study, 86.7% enrolled, 12.7% declined, and 0.6% were ineligible. Of 877 participants enrolled, 272 were pre-implant (of whom 88% completed assessments; "respondents") and 605 were post-implant (of whom 74% completed assessments). Only 14% of respondents reported difficulty completing the questionnaires, 54% had previously used an iPad to complete questionnaires, and 62% reported that their experience was "as expected." Respondents qualitatively described both positive (e.g., value of research) and negative (e.g., too much time) research experiences, difficulties completing questionnaires (e.g., online platform, health literacy issues), and provided recommendations for the questionnaires and delivery. CONCLUSIONS: Participants enjoyed participating in HRQOL research focused on MCS and had unique perspectives for improving the questionnaires. It is important to minimize the burden of participation and critical to be flexible to meet participant preferences for research engagement. TRIAL REGISTRATION: NCT03044535 (accessible at https://clinicaltrials.gov/ct2/show/NCT03044535 ), registered February 7, 2017.

Mesh complications after total vs supracervical laparoscopic hysterectomy at time of minimally invasive sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: Our objective was to compare mesh exposure rates (4 months and 1 year) after total (TLH) vs supracervical (SLH) laparoscopic hysterectomy at time of minimally invasive sacrocolpopexy (SCP). Secondary outcomes included 30-day complications and midurethral mesh exposure rates. METHODS: This a retrospective cohort study at a tertiary care referral center from 2011 to 2018. Subjects were identified using Current Procedural Terminology codes. Demographics, operative characteristics, and perioperative complications were abstracted from medical records. RESULTS: Four hundred three women met the inclusion criteria: 91 SLH+SCP and 312 TLH+SCP. Median follow-up was 52 weeks with an overall mesh exposure rate of 1.5%. Follow-up was available for 90% of patients at 4 months and 51% at 1 year. Half of patients had lightweight mesh (n = 203), and half had ultralightweight mesh (n = 200). Vaginal mesh fixation was performed with permanent suture in 86% (n = 344) and delayed absorbable suture in 14% (n = 56) of patients. At 4 months, vaginal mesh exposure rates did not differ between groups (0% SLH vs 1% TLH, p = 1.00). All mesh exposures in the study period occurred with lightweight mesh in the TLH arm. No differences were noted in 1-year mesh exposure rates, 30-day perioperative complications (p = 0.57), or midurethral mesh exposure rates at 4 months (p = 0.35) and 1 year (p = 1.00) between groups. CONCLUSIONS: Short-term mesh exposure following SCP with ultralightweight and lightweight polypropylene mesh is rare regardless of type of hysterectomy and much lower than reported in earlier studies with heavier weight mesh. These data suggest TLH at the time of SCP is a safe option in appropriately counseled patients.

Psychosocial profiles and longitudinal achievement of optimal cardiovascular risk factor levels: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Psychosocial factors are associated with the achievement of optimal cardiovascular disease risk factor (CVDRF) levels. To date, little research has examined multiple psychosocial factors simultaneously to identify distinguishing psychosocial profiles among individuals with CVDRF. Further, it is unknown whether profiles are associated with achievement of CVDRF levels longitudinally. Therefore, we characterized psychosocial profiles of individuals with CVDRF and assessed whether they are associated with achievement of optimal CVDRF levels over 15 years. We included 1148 CARDIA participants with prevalent hypertension, hypercholesterolemia and/or diabetes mellitus in 2000-2001. Eleven psychosocial variables reflecting psychological health, personality traits, and social factors were included. Optimal levels were deemed achieved if: Hemoglobin A1c (HbA1c) < 7.0%, low-density lipoprotein (LDL) cholesterol < 100 mg/dl, and systolic blood pressure (SBP) < 140 mm Hg. Latent profile analysis revealed three psychosocial profile groups "Healthy", "Distressed and Disadvantaged" and "Discriminated Against". There were no significant differences in achievement of CVDRF levels of the 3 targets combined across profiles. Participants in the "Distressed and Disadvantaged" profile were less likely to meet optimal HbA1c levels compared to individuals in the "Healthy" profile after demographic adjustment. Associations were attenuated after full covariate adjustment. Distinct psychosocial profiles exist among individuals with CVDRF, representing meaningful differences. Implications for CVDRF management are discussed.

Virtual Delivery of Therapeutic Assessment: An Empirical Case Study.

The Therapeutic Assessment (TA) model of psychological assessment has grown in use due to the demonstrated benefits to clients. However, to date, there have been no published articles on how conducting TA virtually may impact the process and experience. The COVID-19 global pandemic led to a rapid increase in virtual delivery of psychological services, including assessments. Assessors adapted procedures to ensure that clients were served ethically, the assessor-client relationship was considered, and the results were deemed valid. This empirical case study was conducted to evaluate test validity, therapeutic alliance, and the clinician's and client's experience of a TA conducted virtually. The validity of test administration was evaluated by experts, who reviewed video of the administration and test results; no concerns regarding integrity and interpretability of the results were identified. Therapeutic alliance, session process, and virtual presence were measured after each session. Both clinician and client reported positive experiences. The overall impact of the TA was evaluated through quantitative assessment of the client's experience and qualitative analysis of interviews. Collectively, this research demonstrates the feasibility of conducting a TA virtually, in an efficacious manner, that leads to positive client outcomes.

Erythropoietin administration expands regulatory T cells in patients with autoimmune hepatitis.

OBJECTIVE: Autoimmune hepatitis (AIH) is a chronic liver disease associated with impaired regulatory T cell (Treg) number and function. Erythropoietin (EPO) is a kidney-produced erythropoietic hormone that has known immune-modulating effects, including Treg induction. Whether EPO administration increases Treg in patients with AIH is unknown. METHODS: We treated six stable AIH patients with a single 1000 IU dose of EPO and comprehensively characterized changes in Treg overall and in Treg subsets before and at 4 and 12 weeks after treatment using mass cytometry (CyTOF) combined with an unbiased clustering approach (Phenograph) based on 22 Treg-relevant cell-surface markers. RESULTS: EPO was well-tolerated and no patients showed significant changes in hematological parameters, liver enzymes, or IgG levels from baseline to 12 weeks following EPO administration. Total Treg and Treg/CD8+ T cell ratios significantly increased at 4 weeks and returned to baseline levels at 12 weeks after EPO injection. We identified 17 Treg subsets of which CD4+CD25HICD127NEG HLADR+ Treg had the highest increase and the most favorable Treg/CD8+ ratio upon EPO treatment. At 12 weeks after EPO administration, the HLADR+ Treg subset also returned to values comparable to those at baseline. Ex vivo assays documented that Treg were functional and the ones isolated at 12 weeks after EPO injection were significantly more suppressive than the ones isolated at baseline. In Treg-depleted assays, EPO did not show a significant effect on IFN-γ+, IL-2+, and IL-17+ CD4+ T cells. CONCLUSION: In stable AIH patients, EPO increases overall Treg and particularly those expressing the high function marker HLA-DR. These results provide the rationale for future studies testing the hypothesis that EPO or EPO analogues improve outcomes of AIH patients by increasing Treg.

Effects of the Family Check-Up 4 Health on Parenting and Child Behavioral Health: A Randomized Clinical Trial in Primary Care.

The Family Check-Up 4 Health (FCU4Health) is an adaptation of the Family Check-Up (FCU) for delivery in primary care settings. While maintaining the original FCU's focus on parenting and child behavioral health, we added content targeting health behaviors. This study evaluated whether the adapted FCU maintained positive effects on parenting (positive behavior support, limit setting, parental warmth) and child behavioral health (self-regulation, conduct problems, emotional problems). Pediatric (6-12 years) primary care patients with a BMI ≥ 85th%ile (n = 240) were recruited from primary care clinics in Phoenix. Children were 75% Latino, 49% female, and 73% Medicaid recipients. This type 2 effectiveness-implementation hybrid trial compared families randomized to FCU4Health (n = 141) or usual care (n = 99). FCU4Health was delivered over a period of 6 months. This study focuses on a priori secondary outcomes included parenting and child behavioral health targets of the original FCU, assessed at baseline and 3, 6, and 12 months. Significant improvements were found for the FCU4Health condition, compared to usual care, in parenting from baseline to the 3-month assessment [ß = .17 (.01; .32)]. Parenting predicted improvements in child self-regulation at 6-months [ß = .17 (.03; .30)], which in turn predicted reductions in conduct problems [ß = - .38 (- .51; - .23)] and emotional problems [ß = - .24 (- .38; - .09)] at 12 months. Ethnicity and language of delivery (English or Spanish) did not moderate these effects. The FCU4Health can improve parenting and child behavioral health outcomes when delivered in primary care.Trial Registration Trial registration number: NCT03013309 ClinicalTrials.gov.

The role of anxiety sensitivity in exercise tolerance and anxiety and depressive symptoms among individuals seeking treatment in cardiopulmonary rehabilitation.

The aim of the current cross-sectional study was to examine the effects of specific anxiety sensitivity (AS) dimensions (AS -Physical, -Cognitive, and -Social concerns) on exercise tolerance (i.e. 6-minute walk test) and factors that interfere with cardiopulmonary rehabilitation (CPR) and exercise adherence (i.e. depression and anxiety symptoms) among individuals seeking treatment in cardiopulmonary rehabilitation (CPR). Participants were 69 individuals (65.2% male, Mage = 63.60, SD = 12.55, Range = 27-85 years) with various cardiovascular or pulmonary conditions meeting criteria for CPR entry, who presented for an intake appointment at an outpatient phase 2 CPR clinic. Higher levels of AS-Physical and-Social concerns were significantly associated with poorer exercise tolerance and greater generalized anxiety symptoms, respectively. Though none of the AS dimensions were significant individual predictors, they were collectively associated with greater depressive symptoms. Future work should assess whether it may be useful to target AS in some patients prior to or throughout CPR.

Extended Nicotine Patch Treatment Among Smokers With and Without Comorbid Psychopathology.

INTRODUCTION: Individuals with psychiatric conditions smoke at higher rates than the general population and may need more intensive treatment to quit. We examined whether or not extended treatment with nicotine patch, combined with behavior counseling, would disproportionally benefit smokers with versus without a lifetime psychiatric condition. METHODS: We conducted a secondary analysis of data from an effectiveness trial of treatment with 12 counseling sessions (48 weeks) and 21-mg nicotine patch (8, 24, or 52 weeks) among 525 adult daily smokers. A structured clinical interview assessed past and current psychiatric disorders (major depression, generalized anxiety disorder, alcohol abuse and/or dependence, and substance abuse and/or dependence), as described in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). Abstinence was bioverified at week 52. Logistic regression evaluated the effect of the psychiatric status × treatment duration interaction on abstinence at week 52, covarying for sociodemographics, baseline psychological symptoms, and treatment adherence. RESULTS: At baseline, 115 (21.9%) participants were diagnosed with one or more psychiatric conditions. The psychiatric status × treatment duration interaction was significant for week 52 abstinence (p = .027). Abstinence rates between smokers with versus without a psychiatric condition in the 24-week treatment arm (9.3% vs. 31.5% abstinent) significantly differed from the 8-week treatment arm (18.8% vs. 22.3%), p = .017. Abstinence rates for smokers with (22.5%) versus without a psychiatric condition (19.7%) in the 52-week treatment arm did not differ from those in the 8-week arm. CONCLUSIONS: Targeted smoking cessation treatment, rather than extending treatment duration, may be especially warranted to optimize treatment for smokers with comorbid mood, anxiety, and substance use disorders. IMPLICATIONS: Individuals with psychiatric conditions smoke at higher rates and have greater difficulty quitting compared to those in the general population, but little is known about how to best optimize treatment for this high tobacco burden population. The present study found that cessation response to extended duration treatment with the transdermal nicotine patch did not differ for smokers with versus without comorbid anxiety, mood, and substance use disorders in a large-scale clinical effectiveness trial. Development of targeted behavioral treatments may be required to optimize abstinence outcomes for this high-risk population, rather than simply extending the duration of pharmacotherapy treatments.

Implementation, feasibility, and acceptability of quality of life therapy to improve positive emotions among patients with implantable cardioverter defibrillators.

Implantable cardioverter defibrillators (ICDs) save lives, but often induce significant psychological distress among patients. Positive psychological constructs are associated with improved outcomes among cardiac patients. In this NHLBI-funded randomized controlled trial, one aim was to evaluate the feasibility and acceptability of a positive psychology intervention (Quality of Life Therapy; QOLT, n = 11), compared to a Heart Healthy Education (HHE) control (n = 10), among ICD patients. A majority of participants across groups attended all 12 sessions (71%) and completed homework assignments (80%). Agreement on participant engagement and interventionist protocol adherence were high, with no differences between groups (ps > 0.20). A greater proportion of QOLT participants rated their sessions was "very" helpful compared to HHE participants (63% vs. 10%, p = 0.19). These initial data support the feasibility and acceptability of QOLT. A larger-scale trial using positive psychology interventions among ICD patients is indicated to determine potential mechanisms underlying the relationship between positive psychological constructs and cardiovascular health.